@article{3fd8e9174eba4b8098038ba27e741e03,
title = "Systems serology detects functionally distinct coronavirus antibody features in children and elderly",
abstract = "The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.",
author = "Selva, {Kevin J.} and {van de Sandt}, {Carolien E.} and Lemke, {Melissa M.} and Lee, {Christina Y.} and Shoffner, {Suzanne K.} and Chua, {Brendon Y.} and Davis, {Samantha K.} and Nguyen, {Thi H.O.} and Rowntree, {Louise C.} and Luca Hensen and Marios Koutsakos and Wong, {Chinn Yi} and Francesca Mordant and Jackson, {David C.} and Flanagan, {Katie L.} and Jane Crowe and Shidan Tosif and Neeland, {Melanie R.} and Philip Sutton and Licciardi, {Paul V.} and Crawford, {Nigel W.} and Cheng, {Allen C.} and Doolan, {Denise L.} and Fatima Amanat and Florian Krammer and Keith Chappell and Naphak Modhiran and Daniel Watterson and Paul Young and Lee, {Wen Shi} and Wines, {Bruce D.} and {Mark Hogarth}, P. and Robyn Esterbauer and Kelly, {Hannah G.} and Tan, {Hyon Xhi} and Juno, {Jennifer A.} and Wheatley, {Adam K.} and Kent, {Stephen J.} and Arnold, {Kelly B.} and Katherine Kedzierska and Chung, {Amy W.}",
note = "Funding Information: We thank all the participants involved in the study, Daniel Pellicci, Jane Batten and Helen Kent for support with the cohort, and Ebene Haycroft and Brendan Watts for Flexmap3D technical assistance. This work was supported by Jack Ma Foundation to K.K., A.W.C. and A.W., the Clifford Craig Foundation to K.L.F. and K.K., NHMRC Leadership Investigator Grant to K.K. (1173871), NHMRC Program Grant to K.K. (1071916), NHMRC Program Grant to D.L.D. (#1132975), NHMRC Program grant to S.J.K. (#1149990), Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to K.K., MRFF Award (#2005544) to K.K., S.J.K., A.W.C., J.J., A.K.W. and Emergent Ventures Fast Grant to A.W.C. A.W.C. is supported by a NHMRC Career Development Fellowship (#1140509), K.K. by NHMRC Senior Research Fellowship (1102792), D.L.D. by a NHMRC Principal Research Fellowship (#1137285). S.J.K. by NHMRC Senior Principal Research Fellowship (#1136322). C.E.S. has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie grant agreement (#792532). L.H. is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from the University of Melbourne. J.A.J. is supported by an NHMRC Early Career Fellowship (ECF) (APP1123673). P.V.L. is supported by a NHMRC CDF2 Fellowship (#1146198). P.S. is supported by DHB Foundation Fellowship. This work is supported by Victorian Government{\textquoteright}s Medical Research Operational Infrastructure Support Program. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-22236-7",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}